Search Results (46)

The Croton genus includes a diverse group of plants with remarkable potential in natural products research, particularly due to their bioactive compounds with hypoglycemic and phytochemical significance. This study examines Croton guatemalensis Lotsy, focusing on its chemical composition and its biological efficacy as a glucose-6-phosphatase inhibitor. Phytochemical analysis led to the isolation and structural elucidation of eleven compounds (1–11), including three new ent−clerodane diterpenes, designated crotoguatenoic acids C (9), D (10), and E (11). The absolute configurations of compounds 9–11 were determined by electronic circular dichroism (ECD) as (5R,8R,9R,10S)-configured ent–clerodanes. High-performance liquid chromatography–mass spectrometry (HPLC–MS/MS) revealed 25 peaks tentatively assigned to terpenoids, flavonoids, and alkaloids, highlighting the species’ chemical diversity. In vitro assays using ethanol–water extract (EWE) and isolated compounds with rat liver microsomes demonstrated inhibitory activity against glucose-6-phosphatase (G6Pase), particularly among ent–clerodane diterpenes (73–96%), with EWE and compounds 1, 4, and 11 showing the highest inhibition. Molecular docking analysis revealed strong interactions between these diterpenoids and the G6PC1 binding pocket, with binding energies comparable to chlorogenic acid (positive control). These findings position C. guatemalensis as a valuable source of bioactive diterpenoids and support the potential of ent-clerodane derivatives as natural G6Pase inhibitors for hyperglycemia management. Full article

Sour meat, a traditional fermented meat product, derives its unique attributes from the flavors developed during the fermentation process. This study systematically investigated the dynamic changes in volatile compounds and bacterial succession in pork sour meat during fermentation (0, 15, 30, and 45 days) using a combination of an electric nose (E-nose), an electric tongue (E-tongue), gas chromatography–ion mobility spectrometry (GC-IMS), gas chromatography–mass spectrometry (GC-MS), and 16S rRNA amplicon sequencing. The results showed that the E-nose and E-tongue effectively distinguished samples across fermentation stages. The pork sour meat was analyzed using GC-IMS and GC-MS, which identified 39 and 81 volatile compounds (VOCs), respectively, primarily esters, alcohols, and aldehydes, with esters being most abundant after 45 days of fermentation. A total of 18 and 25 volatile compounds, respectively, were identified by GC-IMS and GC-MS as differential VOCs (p < 0.05, VIP > 1) of the pork sour meat. α-diversity increased in both species’ richness and diversity over the course of fermentation, while β-diversity analysis further differentiated samples across stages. Firmicutes dominated the bacterial community, with Staphylococcus, Lactobacillus, and Weissella as the main genera. Pearson correlation analysis revealed distinct associations between bacteria and volatiles: Staphylococcus was positively associated with butyl acetate-D, ethyl acetate, isoamyl acetate, dihydroactinidiolide, and (E)-2-heptenal, while Lactobacillus and Weissella were positively associated with acetic acid. Additionally, Weissella showed positive correlations with eight volatile compounds: acetic acid, nonanal, benzyl alcohol, ethyl crotonate, isoamyl acetate, dihydroactinidiolide, octanal, and ethyl acetate. This study provides a comprehensive understanding of volatile compound evolution and bacterial succession in pork sour meat, thereby offering a scientific basis for understanding and regulating its flavor quality. Full article

Croton tiglium L. seeds, a component of many recipes of Thai traditional medicine (TTM), had to undergo the Thai traditional detoxification process (TDP) before being used. However, this detoxification process has never been scientifically proven for its effectiveness. Thus, this research aimed to investigate the effects of TDP on purgative effect and acute toxicity, as well as the identification of some chemical constituents in C. tiglium seeds before (CB) and after (CA) treatment. The purgative effect and acute toxicity of CB and CA powders were evaluated using Wistar rats. The amounts of phorbol-12-myristate-13-acetate (PMA) and crotonic acid in the CB and CA powders were determined using HPLC. The results showed no acute toxicity in the rats administered CB and CA powders at doses of 300–2000 mg/kg of body weight (BW). However, CB and CA caused a dose-dependent increase in the number of fecal pellets as well as an increase in the amount of wet and dry feces. Interestingly, only CB, at the dose of 100 mg/kg, caused a significant purgative effect. The TDP was also found to affect the amounts of PMA and crotonic acid. While the amount of PMA in C. tiglium seed powder decreased from 1.59 mg/g in CB to 1.26 mg/g in CA, the amount of crotonic acid decreased from 0.001 mg/g in CB to an undetectable level in CA. This investigation demonstrated that TDP not only reduced the purgative effect and toxicity of croton seeds but also the amounts of PMA and crotonic acid. Full article

Background: The natural compounds caracasine acid (1) and its methyl ester, caracasine (2), isolated from the flowers of Croton micans, are effective against several tumor cell lines. Five semi-synthetic derivatives (3–7) were synthesized based on these structures. The study aimed to evaluate the cytotoxic activity of these compounds in 2D and spheroid cultures. Methods: The assays were performed in a panel of 12 human cell lines, 8 cancer and 4 normal cell lines. The compounds were evaluated on spheroids derived from the HCT116, HCT116 p53 knockout (p53KO), A549, and U2OS cell lines, as well as mixed spheroids comprising tumor cells and normal fibroblasts. Results: The parent compound (1), the natural ester (2), and two novel derivatives, the anhydride (7) and the cyclohexanol ester (3), demonstrated cytotoxicity against different leukemic cells and HCT116, HCT116 p53 knockout (p53KO), A549, and U2OS cell lines in conventional two-dimensional cultures. Peroxide formation, however, was significantly higher in leukemic cell lines (p < 0.01) in 2D culture as compared with the other tumor cell lines. The compounds did not induce cell death in spheroid cultures; caspases 8, 9, and 3 were not activated upon treatment. Conclusions: These findings indicate potential applications in leukemia treatment, albeit with limited efficacy against solid tumors. Full article

(R)-3-aminobutyric acid is an important raw material for dolutegravir production, which is a key antiretroviral medicine for AIDS treatment. Currently, the industrial production of (R)-3-aminobutyric acid relies on chiral resolution methods, which are plagued by high pollution and low yield efficiency. Here, we report an efficient pathway for (R)-3-aminobutyric acid production via engineered aspartase-driven biotransformation in recombinant E. coli. The engineered aspartase mutants, obtained through rational design based on catalytic mechanisms, were specifically employed to catalyze the production of (R)-3-aminobutyric acid from crotonic acid. The engineered T187L/N142R/N326L aspartase mutant exhibited the highest enzyme activity of 1516 U/mg. Through cell permeabilization, the system achieved (R)-3-aminobutyric acid yield of 287.6 g/L (96% productivity) within 24 h. Subsequent scale-up in a 7 L fermenter achieved a final product yield of 284 g/L (95% productivity) within 24 h. Economic balance showed that the cost of industrial production (¥116.21/kg) is about 1/4 of the laboratory production (¥479.76/kg). In summary, the engineered aspartase-mediated bioconversion pathway using recombinant E. coli offers an industrially viable approach for (R)-3-aminobutyric acid production, featuring mild reaction conditions, environmental sustainability, streamlined processing, high yield, and cost-effective substrates. Full article

Phytochemical investigation and bioactivity evaluation of terpenoids from the Croton species were conducted. The chemical composition of C. sylvaticus was explored using chemical phytochemical screening techniques and dereplication of ¹³C NMR data using MixONat software (v. 1.0.1). Natural products with diverse structural features were identified in the dichloromethane extract of trunk bark. These include monoterpenoids, sesquiterpenoids, diterpenoids, triterpenoids, along with other minor metabolites, such as steroids, saponins, and fatty acids. Further purification of this extract led to the isolation of three major secondary metabolites, acetyl aleuritolic acid, caryophyllene oxide, and phytol. These secondary metabolites were reported for the first time in C. sylvaticus. The isolated compounds were structurally compared to known anticancer terpenoids previously identified in two other Congolese Croton species. Through molecular docking studies, the predicted binding affinities of the identified compounds were assessed, and possible structure–activity relationships (SAR) were proposed. Two structurally characterized receptors—the human androgen receptor (HAR, PDB ID: 1E3G) and hypoxia-inducible factor 1-alpha (HIF-1α, PDB ID: 3KCX), known for their involvement in cancer-related pathways, were used for molecular docking investigations. Among the tested compounds, 1, 2, 3, and 12 were identified as having strong-to-moderate predicted binding affinities to both protein targets, along with favorable drug-like properties according to the ADMET analysis. This investigation could justify the use of Croton plants in traditional medicine. In addition, our study highlights the potential of the Congolese Croton species as sources of bioactive secondary metabolites. Full article

Earias insulana Boisd. (Lepidoptera: Nolidae) is a major pest of cotton and other crops in Egypt, and the widespread use of insecticides has led to resistance. This study evaluates, for the first time, the bioactivity of Croton tiglium (Malpighiales: Euphorbiaceae) oil and its nano-emulsion (CTNE) against 25 newly hatched larvae of E. insulana Boisd. We assessed their biological effects across different developmental stages and performed histological and ultrastructural examinations. Gas–liquid chromatography (GLC) identified several bioactive compounds in C. tiglium oil crushed dry seeds, including fatty acids, hydrocarbons, and sterols. CTNE showed excellent quality with a zeta potential of −17.7 mV, an average particle size of 54.28 nm, and spherical droplets of 42.42 nm in diameter. The LC₅₀ values for C. tiglium oil and CTNE were 9.02% and 2.70%, respectively. Both treatments significantly impacted the biological characteristics of E. insulana Boisd., including reduced larval and pupal weight, lower adult emergence, decreased fecundity, and increased mortality. Histologically, there was epithelial cell hypotrophy and detachment, while ultrastructural damage included chromatin condensation, nuclear envelope folding, and mitochondrial damage, indicating apoptotic degeneration. These findings suggest C. tiglium oil and CTNE as potential, safe alternatives to chemical insecticides. Full article

Breast cancer progression is strongly influenced by estrogen receptor-α (ERα), a ligand-activated transcription factor that regulates hormone binding, DNA interaction, and transcriptional activation. ERα plays a key role in promoting cell proliferation in breast tissue, and its overexpression is associated with the advancement of breast cancer through estrogen-mediated signaling pathways. Targeting ERα is, therefore, a promising therapeutic strategy for breast cancer. However, there are currently no phytochemical-based drug candidates approved for effectively inhibiting breast cancer progression driven by elevated ERα expression. This study aims to identify phytochemical inhibitors from Croton bonplandianum against ERα using pharmacoinformatics approaches. Eighty-three bioactive compounds from C. bonplandianum were retrieved from the IMPPAT (Indian Medicinal Plants, Phytochemistry, and Therapeutics) database and screened through molecular docking for their binding affinity to ERα. The top candidates were further evaluated through molecular dynamics simulations, ADME analysis, toxicity assessment, and quantum mechanics-based DFT calculations. The thermodynamic properties and HOMO-LUMO energy gap values indicated that the selected compounds were both stable and active. Among them, 2,3-oxidosqualene (CID-5366020) and 5,8,11-eicosatriynoic acid, trimethylsilyl ester (CID-91696396) demonstrated the most potent inhibitory activity against ERα. These findings suggest that these compounds have significant potential as therapeutic agents for breast cancer treatment by targeting ERα. Full article

Background: Previous studies of the hydroethanolic extract of Virola elongata inner stem bark (HEVe) have demonstrated its antioxidant, gastroprotective, and antiulcer properties, but have not evaluated its anti-inflammatory potential. Methods: HEVe was obtained by maceration and phytochemically analyzed. Its systemic anti-inflammatory activity was assessed by its effect on lipopolysaccharide (LPS)-induced peritonitis in mice. HEVe gel (HEgVe) was employed to evaluate topical anti-inflammatory activity by measuring the ear edema resulting from croton-oil-induced dermatitis in mice. A cell viability assay was conducted to determine the non-cytotoxic concentrations of the HEVe. RAW 264.7 cells were stimulated by LPS to determinate cytokine and nitric oxide production. Results: A phytochemical analysis of the HEVe revealed the presence of phenolic acids, neolignans, flavonoids, and monomeric catechins. The oral treatment of acute peritonitis with HEVe reduced the total leukocytes, neutrophils, TNF-α, and IL-1β and elevated IL-10 levels. The application of the HEgVe reduced local edema. The HEVe on the RAW 264.7 cells exhibited no cytotoxicity, and the cells with HEVe displayed reduced TNF-α, IL-1β, and NO levels and increased IL-13 levels. Conclusions: HEVe demonstrated systemic and topical multitarget anti-inflammatory activity, likely due to the combined effects of secondary metabolites. HEVe emerges as a promising herbal remedy for inflammation with minimal cytotoxicity, emphasizing its potential therapeutic significance. Full article

Over the years, the world has continued to be plagued by type 2 diabetes (T2D). As a lifestyle disease, obese individuals are at higher risk of developing the disease. Medicinal plants have increasingly been utilized as remedial agents for managing metabolic syndrome. The aim of the present study was to investigate the in vitro anti-hyperglycemic and anti-lipidemic potential of Croton gratissimus herbal tea infusion. The inhibitory activities of C. gratissimus on carbohydrate (α-glucosidase and α-amylase) and lipid (pancreatic lipase) hydrolyzing enzymes were determined, and the mode of inhibition of the carbohydrate digestive enzymes was analyzed and calculated via Lineweaver–Burk plots and Michaelis Menten’s equation. Its effect on Advanced Glycation End Product (AGE) formation, glucose adsorption, and yeast glucose utilization were also determined. High-performance liquid chromatography (HPLC) was used to quantify the possible phenolic compounds present in the herbal tea infusion, and the compounds were docked with the digestive enzymes. C. gratissimus significantly (p < 0.05) inhibited α-glucosidase (IC₅₀ = 60.56 ± 2.78 μg/mL), α-amylase (IC₅₀ = 35.67 ± 0.07 μg/mL), as well as pancreatic lipase (IC₅₀ = 50.27 ± 1.51 μg/mL) in a dose-dependent (15–240 µg/mL) trend. The infusion also inhibited the non-enzymatic glycation process, adsorbed glucose effectively, and enhanced glucose uptake in yeast cell solutions at increasing concentrations. Molecular docking analysis showed strong binding affinity between HPLC-quantified compounds (quercetin, caffeic acid, gallic acid, and catechin) of C. gratissimus herbal tea and the studied digestive enzymes. Moreover, the herbal tea product did not present cytotoxicity on 3T3-L1 cell lines. Results from this study suggest that C. gratissimus herbal tea could improve glucose homeostasis and support its local usage as a potential anti-hyperglycemic and anti-obesogenic agent. Further in vivo and molecular studies are required to bolster the results from this study. Full article

In this study, changes in volatile compounds co-fermented by different Pichia kluyveri with Saccharomyces cerevisiae were analyzed using GC-IMS and compared with S. cerevisiae fermentation, to investigate the production of aroma in mulberry wine during the fermentation process. A total of 61 compounds were accurately identified, including 21 esters, 10 alcohols, 8 aldehydes, 6 ketones, and 19 other volatiles. Compared with the single strain fermentation (S. cerevisiae), the content of 2-methylpropyl acetate, allyl Isothiocyanate, ethyl crotonate, isobutyl propanoate, and butyl 2-methylbutanoate, co-fermentation groups (S. cerevisiae with different P. kluyveri) showed a significant decrease. Alcohols, aldehydes, ketones, and organic acid were lower in both the F(S-P1) and F(S-P2) groups than in the F(S) group throughout fermentation. The 2-methylpentanoic acid only was contained in the F(S) group. The co-fermentation with different P. kluyveri could also be well distinguished. The content of Benzaldehyde and 4-methylphenol in the F(S-P1) group was significantly lower than that in the F(S-P2) group. The PCA results revealed effective differentiation of mulberry wine fermented by different fermentation strains from GC-IMS. The result showed that P. kluyveri could establish a new flavor system for mulberry wine, which plays a crucial role in enhancing the flavor of fruit wine. Full article

The development of antimicrobial resistance has increased the prevalence of infectious diseases, causing a global health problem that accounts for over 4.95 million deaths worldwide annually. The side effects associated with current antibiotics prompt a crucial need to search for effective and safe antimicrobial agents. In this study, silver nanoparticles (AgNPs) were prepared by chemical reduction method using silver nitrates as a metallic precursor and Croton macrostachyus bark aqueous extract as a reducing and capping agent. The nanoparticles were further functionalized using C. macrostachyus-based activated carbon (CAC) to generate nanocomposites (CAC-AgNPs). The nanomaterials were characterized by ultraviolet-visible (UV–vis) absorption spectra and Fourier transform infrared (FTIR) spectra. The antibacterial activity of the as-prepared nanomaterials was evaluated against an array of bacterial strains by microdilution method, whereas their cytotoxicity profile was evaluated using Vero cells (human mammalian cells). Antibacterial mechanistic studies of active nanomaterials were carried out through bacterial growth kinetics, nucleic acid leakage tests, and catalase inhibition assays. As a result, the as-prepared nanomaterials exhibited antibacterial activity against an array of bacterial strains (minimum inhibitory concentration (MIC) range: 62.5 to 500 µg/mL), the most susceptible being Escherichia coli and Staphylococcus aureus. Cytotoxicity studies of the nanomaterials on Vero cells revealed that the nanocomposite (median cytotoxic concentration (CC₅₀): 213.6 µg/mL) was less toxic than its nanoparticle (CC₅₀ value: 164.75 µg/mL) counterpart. Antibacterial mechanistic studies revealed that the nanomaterials induced (i) bacteriostatic activity vis à vis E. coli and S. aureus and (ii) inhibition of catalase in these bacteria. This novel contribution regarding the antibacterial mechanisms of action of silver nanocomposites from C. macrostachyus-based activated carbon may contribute to our understanding of the antibacterial action of these biomaterials. Nevertheless, more chemistry and in vivo experiments as well as in depth antibacterial mechanistic studies are warranted for the successful utilization of these antibacterial biomaterials. Full article

Capsaicin stress, along with salt stress, could be considered the main stressors for lactic acid bacteria in traditional fermented pepper products. Until now, insufficient attention has been paid to salt stress, while the effect of capsaicin on the aroma-producing properties of Lactobacillus plantarum (L. plantarum) is unclear. The present study attempted to illustrate the effect of capsaicin stress on the aroma-producing properties of L. plantarum CL-01 isolated from traditionally fermented peppers based on E-nose and GC–IMS. The results showed that E-nose could clearly distinguish the overall flavor differences of L. plantarum CL-01 under capsaicin stress. A total of 48 volatile compounds (VOCs) were characterized by means of GC–IMS, and the main VOCs belonged to acids and alcohols. Capsaicin stress significantly promoted L. plantarum CL-01 to produce alpha-pinene, ethyl crotonate, isobutyric acid, trans-2-pentenal, 2-methyl-1-butanol, 3-methyl-3-buten-1-ol, 1-penten-3-one, 2-pentanone, 3-methyl-1-butanol-D, and 2-heptanone (p < 0.05). In addition, under capsaicin stress, the contents of 1-penten-3-one, 3-methyl-3-buten-1-ol, 5-methylfurfuryl alcohol, isobutanol, 2-furanmethanethiol, 2,2,4,6,6-pentamethylheptane, 1-propanethiol, diethyl malonate, acetic acid, beta-myrcene, 2-pentanone, ethyl acetate, trans-2-pentenal, 2-methylbutyl acetate, and 2-heptanone produced by L. plantarum CL-01 were significantly increased along with the fermentation time (p < 0.05). Furthermore, some significant correlations were observed between the response values of specific E-nose sensors and effective VOCs. Full article

“Heptil” (unsymmetrical dimethylhydrazine—UDMH) is extensively employed worldwide as a propellant for rocket engines. However, UDMH constantly loses its properties as a result of its continuous and uncontrolled absorption of moisture, which cannot be rectified. This situation threatens its long-term usability. UDMH is an exceedingly toxic compound (Hazard Class 1), which complicates its transportation and disposal. Incineration is currently the only method used for its disposal, but this process generates oxidation by-products that are even more toxic than the original UDMH. A more benign approach involves its immediate reaction with a formalin solution to form 1,1–dimethyl-2-methylene hydrazone (MDH), which is significantly less toxic by an order of magnitude. MDH can then be polymerized under acidic conditions, and the resulting product can be burned, yielding substantial amounts of nitrogen oxides. This review seeks to shift the focus of MDH from incineration towards its application in the synthesis of relatively non-toxic and readily available analogs of various pharmaceutical substances. We aim to bring the attention of the international chemical community to the distinctive properties of MDH, as well as other hydrazones (such as glyoxal, acrolein, crotonal, and meta-crolyl), wherein each structural fragment can initiate unique transformations that have potential applications in molecular design, pharmaceutical research, and medicinal chemistry. Full article

Actinidia arguta wine is a low-alcoholic beverage brewed from A. arguta with a unique flavor and sweet taste. In this study, the basic physicochemical indicators, color, organic acid, and volatile aroma components of wines made from the A. arguta varieties ‘Kuilv’, ‘Fenglv’, ‘Jialv’, ‘Wanlv’, ‘Xinlv’, ‘Pinglv’, ‘Lvbao’, ‘Cuiyu’, ‘Tianxinbao’, and ‘Longcheng No.2’ were determined, and a sensory evaluation was performed. The findings show that ‘Tianxinbao’ produced the driest extract (49.59 g/L), ‘Kuilv’ produced the most Vitamin C (913.46 mg/L) and total phenols (816.10 mg/L), ‘Jialv’ produced the most total flavonoids (477.12 mg/L), and ‘Cuiyu’ produced the most tannins (4.63 g/L). We analyzed the color of the A. arguta wines based on CIEL*a*b* parameters and found that the ‘Kuilv’ and ‘Longcheng No.2’ wines had the largest L* value (31.65), the ‘Pinglv’ wines had the greatest a* value (2.88), and the ‘Kuilv’ wines had the largest b* value (5.08) and C*_ab value (5.66) of the ten samples. A total of eight organic acids were tested in ten samples via high-performance liquid chromatography (HPLC), and we found that there were marked differences in the organic acid contents in different samples (p < 0.05). The main organic acids were citric acid, quinic acid, and malic acid. The aroma description of a wine is one of the keys to its quality. A total of 51 volatile compounds were identified and characterized in ten samples with headspace gas chromatography-ion mobility spectrometry, including 24 esters, 12 alcohols, 9 aldehydes, 3 aldehydes, 2 terpenes, and 1 acid, with the highest total volatile compound content in ‘Fenglv’. There were no significant differences in the types of volatile compounds, but there were significant differences in the contents (p < 0.05). An orthogonal partial least squares discriminant analysis (OPLS-DA) based on the odor activity value (OAV) showed that ethyl butanoate, ethyl pentanoate, ethyl crotonate, ethyl isobutyrate, butyl butanoate, 2-methylbutanal, ethyl isovalerate, and ethyl hexanoate were the main odorant markers responsible for flavor differences between all the A. arguta wines. Sensory evaluation is the most subjective and effective way for consumers to judge A. arguta wine quality. A quantitative descriptive analysis (QDA) of the aroma profiles of ten grapes revealed that the ‘fruity’ and ‘floral’ descriptors are the main and most essential parts of the overall flavor of A. arguta wines. ‘Tianxinbao’ had the highest total aroma score. The flavor and quality of A. arguta wines greatly depend on the type and quality of the A. arguta raw material. Therefore, high-quality raw materials can improve the quality of A. arguta wines. The results of the study provide a theoretical basis for improving the quality of A. arguta wines and demonstrate the application prospects of HS-GC-IMS in detecting A. arguta wine flavors. Full article